title: Gabapentin alleviates facet-mediated pain in the rat through reduced neuronal hyperexcitability and astrocytic activation in the spinal cord.
abstract: Although joint pain is common, its mechanisms remain undefined, with little known about the spinal neuronal responses that contribute to this type of pain. Afferent activity and sustained spinal neuronal hyperexcitability correlate to facet joint loading and the extent of behavioral sensitivity induced after painful facet injury, suggesting that spinal neuronal plasticity is induced in association with facet-mediated pain. This study used a rat model of painful C6-C7 facet joint stretch, together with intrathecal administration of gabapentin, to investigate the effects of one aspect of spinal neuronal function on joint pain. Gabapentin or saline vehicle was given via lumbar puncture prior to and at 1 day after painful joint distraction. Mechanical hyperalgesia was measured in the forepaw for 7 days. Extracellular recordings of neuronal activity and astrocytic and microglial activation in the cervical spinal cord were evaluated at day 7. Gabapentin significantly (P = .0001) attenuated mechanical hyperalgesia, and the frequency of evoked neuronal firing also significantly decreased (P < .047) with gabapentin treatment. Gabapentin also decreased (P < .04) spinal glial fibrillary acidic protein expression. Although spinal Iba1 expression was doubled over sham, gabapentin did not reduce it. Facet joint-mediated pain appears to be sustained through spinal neuronal modifications that are also associated with astrocytic activation.
  
  
  CONCLUSIONS
  Intrathecal gabapentin treatment was used to investigate behavioral, neuronal, and glial response in a rat model of painful C6-C7 facet joint stretch. Gabapentin attenuated mechanical hyperalgesia, reduced evoked neuronal firing, and decreased spinal astrocytic activation. This study supports that facet joint pain is sustained through spinal neuronal and astrocytic activation.
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Ling
authors.initials: L
authors.lastname: Dong
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Crosby
authors.forename: Beth A
authors.initials: BA
authors.lastname: Winkelstein
mesh_terms: D000588:Amines / Q000008:administration & dosage*; D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D018771:Arthralgia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage*; D000077206:Gabapentin; D007278:Injections, Spinal; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D021801:Zygapophyseal Joint / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage*
chemical_list: D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin
keywords: Neuronal hyperexcitability; astrocyte; facet joint; gabapentin; spinal cord